The research program is directed towards studying the biochemistry and physiology of secretion at the nerve terminal with particular emphasis on intracellular ion transients, modulation of secretion, and mechanism of exocytotic secretion. The neurohypophysial nerve terminals and the squid optic lobe and giant synapse served as experimental models. Experiments included studies on secretion of vasopressin and oxytocin from isolated neurosecretosomes, and measurement of calcium ion transients in the nerve terminals using high resolution fluorescence microscopy. Neurosecretosomes respond to depolarizing stimuli with markedly elevated secretion which inactivates on prolonged depolarizations. Depolarization causes calcium increase in the nerve terminal cytoplasm via at least two different types of voltage-activated calcium channels, and calcium remains elevated as long as depolarization exists. Secretion, on the other hand, undergoes inactivation despite the elevated cytoplasmic calcium levels. Calcium ions entering the terminal via specific calcium channels are more efficacious in initiating secretion. A study of synaptic vesicle associated proteins in the squid resulted in the characterization of low molecular weight GTP-binding proteins and synaptobrevin. A cell-free system and a permeabilized cell model are being developed to study the exocytotic process.